High-dose chemotherapy (CTM) for breast cancer

Abstract

Summary:We designed and implemented a new mitoxantronebased high-dose chemotherapy regimen to minimize pulmonary injury (seen in carmustine-based regimens) in patients with breast cancer. One hundred and ninetyone breast cancer patients (99 stage II/IIIA; 27 stage IIIB; 65 stage IV responsive to conventional-dose chemotherapy) were treated with high-dose chemotherapy (CTM) delivered over 4 days (cyclophosphamide (6 g/m 2 ), thiotepa (600 mg/m 2 ), and mitoxantrone (24-60 mg/m 2 )) followed by autologous hematopoietic stem cell rescue. Stage II/III patients received chest wall radiation and tamoxifen (if hormone-receptor positive) after CTM. The 5-year event-free survival (EFS) for stage II/IIIA patients with 10 or more involved axillary lymph nodes (n = 80) was 62 ؎ 12%. Hormone receptor-positive patients with 10 or more nodes did significantly better than negative patients. The EFS for stage IIIB patients at 5 years was 44 ؎ 19%; for stage IV patients at 5 years was 17 ؎ 10%. Stage IV patients achieving complete response in viscera and/or soft tissue prior to CTM did significantly better than those achieving a partial response. There were six (3%) treatment-related deaths including two due to diffuse alveolar hemorrhage. There were no episodes of delayed interstitial pneumonitis. There were six severe cardiac events in 91 patients (6.6%) but none after instituting mitoxantrone dose-adjustment in the final 100 patients. We conclude that CTM is associated with a low treatment-related mortality and little pulmonary toxicity. CTM produces excellent outcomes in stage II/IIIA patients with 10 or more involved axillary lymph nodes. Bone Marrow Transplantation (2000) 26, 257-268.

High-Dose Chemotherapy of Cyclophosphamide, Thiotepa, and Carboplatin (CTCb) Followed by Autologous Stem-Cell Transplantation for Metastatic Breast Cancer Patients: A 6-Year Follow-Up Result

“…Additionally, the patients achieving a CR to induction chemotherapy showed significantly higher 5-year PFS rate than those patients who were not in CR prior to their ASCT (33% vs. 9%). Other authors have reported similar results (5,10,22,24), and interestingly, the induction regimen with CAF showed a tendency for a better PFS and OS. All the patients whose induction regimens were TP received this regimen as a second-or third-line chemotherapy after prior use of CAF for metastatic disease, while the remaining patients received CAF as first-line treatment (except for one patient).…”

Cardiac toxicity of high-dose chemotherapy

“…47 In another study, administration of HD cyclophosphamide at the maximum tolerated dose (ie 200 mg/kg) divided into only two daily fractions may have played a role in determining a 25% incidence of CHF with one treatment-related death, besides the potential contribution of HD mitoxantrone in patients previously exposed to anthracyclines. 48 Overall, it is worth noting that considerable differences in cardiotoxicity profile were observed between combinations of cytarabine [39][40][41][42][43][44][45] or HD mitoxantrone, [47][48][49][51][52][53] and HD cyclophosphamide for relatively minor differences in sequence and schedule of administration.…”

Secondary acute leukemia following mitoxantrone-based high-dose chemotherapy for primary breast cancer patients

“…[16][17][18][19] Mitoxantrone is part of several high-dose chemotherapy regimens followed by autologous stem cell transplantation in breast cancer patients. [20][21][22][23] In the present study, we evaluate the incidence of secondary MDS/AML in 305 breast cancer patients after mitoxantrone-based high-dose conditioning regimens, followed by autologous stem cell transplantation in a joint analysis of the Solid Tumor Working Party of the European Group for Blood …”